RESUMO
Numerous investigations have been reporting the involvement of GM1 ganglioside in central nervous system development and memory formation. The effects of neonatal treatment with GMI ganglioside on the performance of adult rats in a plus-maze discriminative avoidance task and old rats in a step-down passive avoidance task were investigated. Rats were injected subcutaneously from day 3 to 15 after birth with 10 mg/kg GM1 or saline. GM1 treatment did not modify indicative landmarks of physical and motor development. Behavioural tasks were carried out when the animals were 4 (discriminative avoidance) or 24 (passive avoidance) months old. Discriminative avoidance conditioning was performed in a modified elevated plus-maze. During the training session, the animals received aversive stimulation (light and hot air blow) in one of the enclosed arms. Tests were performed 7, 14 and 21 days after conditioning (tests 1, 2 and 3), in the absence of the aversive stimulation. In all tests, GM1-treated animals spent less time in the aversive arm than in the non-aversive enclosed arm. Control animals, however, spent a shorter time in the aversive arm only in tests 1 and 2. Passive avoidance conditioning was performed in an acrylic box with a grid floor, that was partially covered by an inclined platform. Animals were placed on the platform and received a 0,5 mA foot shock when stepped down. A test was performed 48 hr later. Latency to step down presented by GM 1-treated animals was significantly higher in the test session, whereas no significant increase in latency to step down was found for control animals. The results suggest a possible action of GM1 on the maturation of the central nervous system that persists during adulthood and ageing.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Gangliosídeo G(M1)/farmacologia , Memória/efeitos dos fármacos , Análise de Variância , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Sistema Nervoso Central/crescimento & desenvolvimento , Feminino , Gangliosídeo G(M1)/administração & dosagem , Injeções Subcutâneas , Masculino , Ratos , Ratos WistarRESUMO
This study examines the effects on open-field and stereotyped behaviour of rats of abrupt withdrawal from repeated treatment with a low (0.03 mg kg-1) dose of haloperidol. Single administration of this low dose of haloperidol significantly increased open-field locomotion without modifying apomorphine (0.5 or 2.0 mg kg-1)-induced stereotyped behaviour. Forty-eight hours after abrupt withdrawal from 0.03 mg kg-1 haloperidol (twice daily for 15 days) a significant decrease in locomotion frequency was observed, but no change was observed in apomorphine-induced stereotypy. Our results suggest that dopamine autoreceptor supersensitivity might be evaluated in a behavioural situation of absence of postsynaptic dopamine receptor supersensitivity.
Assuntos
Comportamento Animal/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Locomoção/efeitos dos fármacos , Comportamento Estereotipado/efeitos dos fármacos , Administração Oral , Animais , Apomorfina/farmacologia , Autorreceptores/efeitos dos fármacos , Autorreceptores/metabolismo , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/administração & dosagem , Interações Medicamentosas , Haloperidol/administração & dosagem , Injeções Intraperitoneais , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Síndrome de Abstinência a SubstânciasRESUMO
The effects of age were studied on a new animal model of tardive dyskinesia, i.e., the quantification of oral dyskinesia in rats repeatedly treated with reserpine. Adult and old rats received two injections of reserpine (0.5 or 1.0 mg/kg s.c.) or vehicle, separated by 48 h. One, 10, 25 and 40 days after the second injection of reserpine or vehicle, the animals were observed for quantification of the behavioral parameters of oral dyskinesia: tongue protrusion and vacuous chewing movement frequencies and duration of twitching of the facial musculature. Phenomenologically, control old rats and reserpine-treated adult animals showed very similar oral dyskinesia. When compared to control adult rats, the significant increase in tongue protrusion frequency induced by reserpine treatment was more persistent in the old rats than in the adult animals. Because it is well known that age increases the persistence of tardive dyskinesia, our data provide further support for the validation of reserpine-induced oral dyskinesia as an animal model of tardive dyskinesia. In addition, the possibility is raised that a common pathophysiological mechanism may underlie tardive dyskinesia and age- and reserpine-induced oral dyskinesia.